The long term objectives of this study are to examine the neural and neurochemical regulation of motor output and respiratory in anuran amphibians. The principal objectives of this study are to determine the roles of peripheral afferent feedback and central neurochemical mechanisms in modulating various types of ventilatory behaviors exhibited by anurans. To carry out the specific aims of this proposal, adult bullfrogs (Rana catesbeiana) will be used as a general model for anuran respiratory control. Frogs typically exhibit three distinct types of ventilatory behaviors: buccal oscillations, lung ventilations and lung inflation cycles. Although each ventilatory behavior is unique, many of the same respiratory muscles are used for each type of behavior, suggesting that the motor output from brainstem cranial motoneurons is precisely modulated to generate each ventilatory motor pattern. It is likely that both peripheral feedback and regulation of central nervous system (CNS) neurotransmission participate in this modulation of motor output; however, the extent to which peripheral and CNS mechanisms participate in this regulation is unclear. Whereas buccal oscillations are generally very rhythmic, lung ventilation has been characterized as "intermittent" or "episodic" because lung ventilation events are unpredictable and do not appear to be rhythmic under most conditions. In this respect, breathing patterns of amphibians are similar in pattern to "periodic" breathing in mammals that occur in certain congenital or pathological conditions. Recent evidence suggests that intermittent lung ventilation is an intrinsic property of the respiratory central patten generator 9CPG), but it is unknown whether separate CPGs regulate the different types of ventilatory patterns in anurans. The specific aims of the proposed research are to, 1) use analytical techniques (phase resetting) to examine the behavior of the anuran respiratory CPG; 2) examine the roles of vagal and hypoglossal cranial nerve feedback in controlling normal respiratory motor patterns and the integration of chemorecept input; and, 3) examine the role of fast excitatory and inhibitory mechanisms within the CNS that may contribute to modulation of respiration motor output. Because anuran respiratory motor patterns exhibit similarities to some abnormal - breathing states in mammals, examination of the control of episodic breathing in anurans may lead to a better understanding of the mechanisms that contribute to periodic breathing.